MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?
Frontiers in Genetics January 1, 2012 Rafael de la Torre, Samanta Yubero‐lahoz, Ricardo Pardo‐lozano et al. 108 citations
The metabolism of amphetamine-like psychostimulants is regulated by the polymorphic enzyme CYP2D6. Methamphetamine acts as a weak substrate and competitive inhibitor of CYP2D6, while MDMA is a high-affinity substrate and potent mechanism-based inhibitor, causing all users to phenocopy the poor metabolizer phenotype regardless of genotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than in vitro studies suggest, with other cytochrome P450 isoenzymes and renal excretion contributing significantly. Overall, the clinical relevance of CYP2D6 polymorphism is lower than predicted by in vitro findings.